Large-Scale Preparation of Iodobenzene Dichloride and Efficient Monochlorination of 4-Aminoacetophenone

Abstract

Large-scale monochlorination of 4-aminoacetophenone using iodobenzene dichloride is described. Special emphasis was given to the characterization of the iodobenzene dichloride and to the development of a practical procedure for handling this agent from the viewpoint of hazards. This process was successfully scaled up in a pilot plant.

Biphasic Chlorination of Iodoarenes to (Dichloroiodo)arenes

“…A year later 5 he developed the most common method [5][6][7][8][9] up to now for preparing ArICl 2 :…”

Advances in Iodine(III)‐Mediated Halogenations: A Versatile Tool to Explore New Reactivities and Selectivities

“…Despite the utility of hypervalent iodine(III) halogenation reagents, such as PhICl 2 ( 1 ) or p ‐TolIF 2 ( 10 ), their broader application, in particular in industrial processes, is very rare. Although transformations using reagent 1 can easily be scaled up to 20 kg, as shown for the aromatic chlorination of p ‐aminoacetophenone ( 54 ; Scheme ) within the synthesis of COX‐2‐selective inhibitors, the particular bottleneck of reagent‐based hypervalent iodine(III) chemistry is its low atom economy.…”

Organic Iodine(I, III, and V) Chemistry: 10 Years of Development at the Medical University of Warsaw, Poland

“…In comparison with the classic Willgerodt method [56][57][58][59], the biphasic chlorination method avoids the inconvenient use of gaseous Cl 2 , hence it is relatively safe. If an oxidant, e.g.…”

“…An active chlorine in statu nascendi, formed in the aqueous phase of the biphasic system, is very quickly deactivated there to form the "ordinary" dichlorine, Cl 2 , which next is readily absorbed and consumed in the organic phase containing ArI to produce there ArICl 2 . Similarly, in the Willgerodt method [56][57][58][59], the stream of this "ordinary" dichlorine, Cl 2 , is passed through solutions of ArI in inert solvents to form there ArICl 2 . Thus, we previously expressed the opinion [12] that "the limits of the scope of the two methods are the same or nearly so."…”

“…Anhydrous conditions previously demanded [57] are not necessary [58]. Quite recently [59], the repeated preparations of PhICl 2 (in 94% crude yield) on a 20 kg scale have been conducted by the direct chlorination of PhI (dissolved in CH 2 Cl 2 ), at -3 to +4 o C; next, it was possible to monochlorinate 4-aminoacetophenone with PhICl 2 on 24.8 kg scale, in 87% yield.…”